People with Type 1 diabetes (T1D) are at high risk for acute and chronic complications that can be minimized by concurrent use of continuous insulin delivery and continuous glucose monitoring (CGM). However, the use of two percutaneous devices is cumbersome and seldom used. We are developing a single subcutaneous catheter that serves both as a CGM and as an insulin cannula. The electrodes and chemicals necessary for CGM are disposed on the outer wall of the cannula. Based on recent animal studies, we now know that the electroactivity of insulin preservatives is incompatible with conventional amperometric sensing technology. In order to minimize interference from these preservatives after bolus delivery, we will work with an organic chemist to identify sensing chemistries that allow detection of glucose oxidation at low redox potentials, where the preservatives have minimal to no electroactivity. The chemistry will either be (a) a redox mediator coordinated within a pyridine or imidazole-based ligand or (b) a horseradish peroxidase-based system designed to measure reduction of H2O2 at negative potentials. Electrochemical screening will take place using solution phase cyclic voltammetry. The chemistry will be optimized to immobilize sensing layers and create a durable sensor: The most promising compounds will be immobilized on Au or Pt indicating electrodes followed by crosslinking to glucose oxidase. The final choice of solid phase chemistry will be based in large part on maximizing the glucose:cresol response ratio, ensuring stable function for at least 4 days, and avoidance of leaching. If a redox mediator is chosen, the outer membrane will be selected to have very low permeability to oxygen due to the fact that oxygen competes with redox mediators. An existing permeation cell will be used to measure oxygen and glucose membrane permeability. In Yucatan pigs, we will assess preservative interference during insulin delivery 1- and 4 days after sensor insertion. The purpose of the second study at 4 days is to determine if sensor sensitivity declines over this period, which would suggest loss of reagents from the sensor. In summary, to minimize device burden in T1D, we will develop and test a sensing chemistry that avoids the large interference one sees from preservatives during insulin boluses, thus allowing CGM and insulin delivery via a single catheter.